The human T cell leukemia virus, HTLV-1, is the etiologic agent of adult T cell leukemia lymphoma. This virus is endemic to several areas of the world and the disease caused by this virus, although rare, is an extremely aggressive neoplasm with a high fatality rate. The T cells transformed by this virus somehow overcome the normal dependence of T cells on the growth factor, interleukin 2 (IL-2), and grow autonomously in its absence. This is despite the fact that these cells do not appear to make their own IL-2 to meet this requirement. The virus encodes two proteins which appear to influence cellular as well as viral gene expression. The tax protein is known to be a transactivator of transcription and to influence cellular as well as viral promoter activity. The second product, the rex protein, has also recently been shown to influence cellular gene expression. Two of these genes known to be upregulated in their expression by tax and rex are those for IL-2 and its receptor. The goal of these studies is to understand how the rex gene product influences IL-2 gene expression and what cellular factors might be involved in the up-regulation. The first specific aim is to determine the target sequences used by the rex protein to increase IL-2 promoter activity. This work includes the introduction of mutations into the IL-2 promoter sequence to identify the regions influenced by the rex protein. The second specific aim is to determine the effect of the rex protein on endogenous IL-2 gene expression. These studies include the construction and use of cell lines inducible for the expression of tax and rex. Specific aim 3 is designed to identify tax and rex affected transcription factors which activate the IL-2 promoter and aim four is to further describe that affect. These experiments will involve gel migration retardation analysis of nuclear factors and RNA stability analysis as well. These studies will aid in the understanding of how this virus causes disease and how T cells infected with this virus escape normal cell growth control mechanisms to grow autonomously in the absence of IL-2. In addition, these studies will provide further insight to the control mechanisms active in normal T cells important to the study of AIDS and other diseases of the immune system. Funds are sought for one undergraduate and one graduate student. The undergraduate student will first be placed under the supervision of a graduate student or post-doctoral fellow. A period of training, at least 6 months to one year in length, will be used to familiarize the student with laboratory and safety procedures and then the student will be given an independent research project designed in conjunction with the P.I. This research project will be directly related to one of the aims presented above. The graduate student will be trained by the P.I. and other students in the lab and will be given an independent research project related to one or more of the aims described above. All students are required to attend and present at weekly lab meetings and journal clubs, and are required to attend research seminars.